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Pleural fluid cell-free DNA integrity index to identify cytologically negative malignant pleural effusions including
Krishna B Sriram1, Vandana Relan, Belinda E Clarke
1UQ Thoracic Research Centre, School of Medicine, The University of Queensland, Queensland, Australia. bajee.sriram@uqconnect.edu.au
Background:
The diagnosis of malignant pleural effusions (MPE) is often clinically challenging, especially if the cytology is negative for malignancy. DNA integrity index has been reported to be a marker of malignancy. The aim of this study was to evaluate the utility of pleural fluid DNA integrity index in the diagnosis of MPE.
Methods:
We studied 75 pleural fluid and matched serum samples from consecutive subjects. Pleural fluid and serum ALU DNA repeats [115bp, 247bp and 247bp/115bp ratio (DNA integrity index)] were assessed by real-time quantitative PCR. Pleural fluid and serum mesothelin levels were quantified using ELISA.
Results:
Based on clinico-pathological evaluation, 52 subjects had MPE (including 16 mesotheliomas) and 23 had benign effusions. Pleural fluid DNA integrity index was higher in MPE compared with benign effusions (1.2 vs. 0.8; p<0.001). Cytology had a sensitivity of 55% in diagnosing MPE. If cytology and pleural fluid DNA integrity index were considered together, they exhibited 81% sensitivity and 87% specificity in distinguishing benign and malignant effusions. In cytology-negative pleural effusions (35 MPE and 28 benign effusions), elevated pleural fluid DNA integrity index had an 81% positive predictive value in detecting MPEs. In the detection of mesothelioma, at a specificity of 90%, pleural fluid DNA integrity index had similar sensitivity to pleural fluid and serum mesothelin (75% each respectively).
Conclusion:
Pleural fluid DNA integrity index is a promising diagnostic biomarker for identification of MPEs, including mesothelioma. This biomarker may be particularly useful in cases of MPE where pleural aspirate cytology is negative, and could guide the decision to undertake more invasive definitive testing. A prospective validation study is being undertaken to validate our findings and test the clinical utility of this biomarker for altering clinical practice.
Insights
The DNA integrity index in pleural fluid shows promise for diagnosing malignant pleural effusions (MPE), especially when cytology is negative. This biomarker aids in identifying MPE and mesothelioma, potentially guiding further diagnostic tests.
Area of Science:
- Oncology
- Pulmonology
- Biomarker Discovery
Background:
- Malignant pleural effusions (MPE) pose diagnostic challenges, particularly with negative cytology.
- DNA integrity index is a potential marker for malignancy.
Purpose of the Study:
- To evaluate the diagnostic utility of pleural fluid DNA integrity index for MPE.
- To assess its role in differentiating MPE from benign effusions.
Main Methods:
- Real-time quantitative PCR was used to measure ALU DNA repeats and calculate the DNA integrity index in pleural fluid and serum.
- ELISA quantified mesothelin levels in pleural fluid and serum.
- 75 pleural fluid and matched serum samples were analyzed.
Main Results:
- Pleural fluid DNA integrity index was significantly higher in MPE (1.2) than in benign effusions (0.8).
- Combining cytology with DNA integrity index improved sensitivity to 81% and specificity to 87%.
- In cytology-negative cases, elevated DNA integrity index had an 81% positive predictive value for MPE.
Conclusions:
- Pleural fluid DNA integrity index is a valuable biomarker for MPE detection, including mesothelioma.
- It is particularly useful in cytology-negative MPE cases.
- Further validation studies are underway to confirm clinical utility.
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